Using Microscopical Analysis Methods
Contract Pharma - October 14, 2014
The integrity of the container system is crucial to the safety of parenteral products. The presence of glass delamination flakes in product solutions is of particular concern. Glass delamination occurs when the inside surface of the vial begins to degrade and eventually very thin glass flakes begin to spall off of the surface and appear in the liquid product. Glass container stability may be affected by a large number of factors, including the vial manufacturing process, post-formation treatments, depyrogenation and sterilization, and interaction with the drug product. The appearance of flakes in solution indicates that there is significant damage to the vial’s internal surfaces and may lead to recalls and lost revenue. It is crucial to evaluate the compatibility and stability of the product with the glass vials during the initial stages of new drug development. Ideally, accelerated stability samples are tested for the presence of glass delamination as part of the drug development.
Microscopy—using both light microscopes and electron microscopy—is a vital tool in the evaluation of parenteral vials for the presence of glass delamination. At McCrone Associates, evaluation of glass delamination in product vials usually includes three stages. First, light microscopy is utilized to determine if potential glass delamination is present in the product solution. If glass delamination-like flakes are observed, chemical analysis (stage 2) is needed to confirm that the flakes are consistent with glass. Typically, scanning electron microscopy with energy dispersive X-ray spectrometry (SEM/EDS) is used to confirm that the flakes are chemically consistent with glass delamination. Transmission electron microscopy (TEM) may be used for extremely thin flakes that are difficult or impossible to analyze using SEM/EDS. The third step is to examine the interior surfaces of the vials for evidence of pitting and flaking.